Dilated cardiomyopathy (DC) is a disease of unknown cause characterized by dilation and impaired function of one or both ventricles. Although the prevalence of this condition is low, approximately 37 per 100,00(), the severity of the disease often leads to cardiac transplantation. Unraveling the etiology of DC will lead to improved prevention and treatment strategies. From a previously funded study we have developed a comprehensive data base for 94 families that have members affected with DC. These data include extensive electrocardiographic and echocardiographic measurements, as well as environmental risk factors. From these data we have estimated that 24% of the index cases with DC were familial (i.e., at least one other first-degree relative had DC). Additional analyses support the hypothesis that genetics plays a major role in the etiology of DC in some of our families. Hence, detailed statistical genetic analyses are now warranted. In Aim 1, we hypothesize that index patients with familial DC differ according to a number of characteristics from index patients without familial disease. Univariate statistical comparisons will be made between familial and non-familial index cases. In Aim 2, we hypothesize that a major gene is segregating in at least some of our families for traits related to DC; segregation analyses will be used to assess a wide variety of traits. In Aim 3, we hypothesize that a linear combination of measured traits related to DC will be useful to discern a single major gene; this will be assessed through pedigree discriminant segregation analysis. In Aim 4, we hypothesize that genetic heterogeneity exists. We will use statistical procedures to classify pedigrees into those segregating for a major gene and those not segregating. The characteristics of index patients will then be compared between those index patients classified as from segregating pedigrees and those classified as from non-segregating pedigrees, in order to determine if measured characteristics can be useful to discriminate genetic cases from non-genetic cases. The results from this project could lead to clinically useful criteria for counseling patients and their families, a better definition of the genetic etiology of DC, and a guide to future genetic linkage studies. Out data resource is unique because of the large number of unselected index patients and their relatives who have had comprehensive evaluations regardless of their medical history. No other resource of this extent is available to assess the genetic etiology of idiopathic dilated cardiomyopathy.